Abstract: Regardless of race, 50 years of age is the current screening recommendations for colorectal cancer (CRC) disease based on an assumption that the prevailing CRC disparities are relatively due to differences in access to quality screening and the post diagnostic therapies. However, several lines of evidence have suggested that in younger age groups, AA have twice the CRC incidence rate as Whites, and their stage- adjusted CRC survival rates are lower than Whites. Given that most CRCs arise from precancerous of adenomatous polyps (adenopolyps) that evolve into invasive adenocarcinoma, it is plausible that certain ?modifying? genes expression may potentially responsible for the observation in AA experience to earlier adenopolyps initiation and more rapid adenopolyps progression to adenocarcinoma. If such is the case, one potential factor in the persistent of CRC disparities may be the race-nonconforming/or neutral age guideline for screening initiation. Studies regarding age-related AA-White differences in CRC progression through the intermediate stages (polyp sizes of tubular, tubulovillous, and villous, and dysplastic histology) are needed. To establish such evidence, it requires genetic alteration study in a modifying gene(s) and a tissue source representing the colorectal adenopolyp prevalence and profile in the population from a large enough autopsy sample size with complete adenopolyps clearance and having complete colorectal adenopolyps documentation. Our study will leverage a unique of 640 colorectal adenopolyp/ cancer cases and 1280 control tissue samples in a frequency matched nested case-control within our lab and Southern Division Co-operative Human tissues Network at University of Alabama collected through previous NIH-funded studies. The sample size has sufficient statistical power to compare AA and Whites on precancerous of colorectal adenopolyps prevalence and cancer-relevant features with difference age strata. These tissue collections are large and well-annotated by micro-dissection. Our laboratory recently demonstrated that there were progressive increase of mitochondrial gene expressions in colorectal adenopolyps and carcinomas when compared to their normal surrounding tissues (accepted paper Tumor Biology #TUBI-16-00926R1), suggesting that certain mt-genes expression are involved in the malignancy of colorectal adenopolyps to invasive adenocarcinoma. Based on these data, the central hypothesis of this project is that over-expression of certain mt-genes play a role in the aggressiveness of precancerous colorectal tumor behavior within younger AA which are reflected in their high incidence and low survival rate of this disease. To test this hypothesis, we will determine the level of mt-genes alterations in colorectal adenopolyps between AA-White subgroups. Also, we will evaluate our results relative to AA-White differences within 10 year age strata and their related features (size, histology, anatomic location, dysplasia status, and adenocarcinoma), as well as body mass index (BMI) using univariate statistical tests, multiple regression and cluster analysis.